The physiology of the mammalian nephron has been extensively examined by micropuncture techniques. Assessment of the factors controlling renal salt and water excretion using micropuncture techniques is difficult, however, because following anesthesia and surgery, salt excretion is reduced to less than 10% of values seen in the awake rat. We have demonstrated that as a consequence of the surgery necessary to prepare the animal for micropuncture plasma volume is markedly reduced from awake values, red cell volume remaining constant. Repletion of the plasma volume to awake animal values (euvolemia) with isoncotic plasma restores salt and water excretion to values appropriate to the dietary history of the animal. Under euvolemic conditions we have found that single nephron filtration rates and glomerular plasma flow rates are 50% higher than those normally reported for the hydropenic rat and are similar to those reported in the conscious animal. Furthermore, fractional volume and total CO2 reabsorption in the proximal convoluted tubule are considerably lower in euvolemia (40% and 75%, respectively) than in hydropenia (50% and 90%, respectively). The data further suggested a preferential reabsorption of NaHCO3 over NaCl following plasma repletion. The objectives of this proposal include: 1) an examination of the site(s) of alteration of electrolyte transport in the euvolemic rat following acute unilateral nephrectomy, 2) an examination of glomerular dynamics in the euvolemic hypertensive rat and the response to antihypertensive agents, and 3) an examination of proximal tubule NaCl, NaHCO3 and volume reabsorption following sodium chloride and sodium bicarbonate loading.